A pharmacokinetic study of ethanol elimination--first pass metabolism and elimination rate

In this study two pharmacokinetic dispositions of ethanol metabolism were investigated. To determine the existence of first pass metabolism (FPM), Japanese male volunteers with and without a low Km isozyme of aldehyde dehydrogenase (ALDH) received 0.1 and/or 0.4 g/kg dose of ethanol either perorally or intravenously. Blood ethanol level was lower and the area under the blood ethanol concentration-time curve (AUC) was smaller under peroral than under intravenous administration, although tantamount doses of ethanol were administered. The difference in AUC between peroral and intravenous administrations was apparent when a lower dose of ethanol was given. These findings were taken to indicate that a significant fraction of ethanol administered perorally was metabolized during absorption before reaching the systemic circulation and that this FPM of ethanol became clearer in smaller ethanol doses. In order to compare the parameters of Widmark's zero-order kinetics and Michaelis-Menten kinetics, sixty-one male volunteers, i.e. 30 subjects with normal ALDH and 31 with a deficiency of it, ingested 0.4 g/kg of ethanol perorally. The elimination phase of blood ethanol-time curve was fitted to a two-compartment open model with Michaelis-Menten elimination kinetics. A significant difference was seen in beta 60 between the normal ALDH group and the deficient one. Vmax in the normal ALDH group was relatively higher than that in the deficient one and Vmax was significantly correlated to beta 60. Km varied widely among the individual subjects. In the case in which high or moderate dose of ethanol is administered, the Widmark's method is sufficient for ethanol elimination studies in clinical and medicolegal practices.